tbuckley/cabot-search huggingface dataset:
Associations between adoption of eHealth management module and optimal control of HbA1c in diabetes patients
Authors: Junjie Huang, Sze Chai Chan, Samantha Ko, Ellen Tong, Clement S. K. Cheung, Wing Nam Wong, Ngai Tseung Cheung, Martin C. S. Wong
Journal: npj Digital Medicine (2023)

In January 2021, the eHealth App was launched in Hong Kong by the Hong Kong government to support the Electronic Health Record Sharing System (eHRSS). A Health Management Module in the eHealth App introduced new functions to record blood pressure, blood sugar, and heart rate, and downloading and sharing records. This study aims to compare the level of glycaemic control between users of the eHealth App and non-users. Type 2 diabetes patients who have joined the eHRSS with existing haemoglobin A1c (HbA1c) level records are recruited. Correlations between predictors and optimal HbA1c control (<7%) are examined using logistic regression analyses. A total of 109,823 participants are included, with 76,356 non-users of eHealth App, 31,723 users of eHealth App, and 1744 users of the eHealth Management Module together with the App. We collect HbA1c values from Jan 2021 to May 2022, and they are 6 months after the use of the App on average. Users of the eHealth Management Module are found to have more optimal HbA1c levels across all subgroups, with the strongest effect observed in younger females (aOR = 1.66, 95% CI = 1.27-2.17). eHealth App usage is also positively associated with optimal HbA1c levels, particularly amongst younger females (aOR = 1.17, 95% CI = 1.08-1.26). Overall, users of eHealth App and eHealth Management Module demonstrate more optimal HbA1c levels when compared with non-users, particularly among younger adults and females. These findings support its potential adoption in diabetes patients. Future studies should examine the impact of eHealth interventions on other clinical targets and diabetes complications.
Immunotherapy of thymic epithelial tumors: molecular understandings and clinical perspectives
Authors: Yong-Qiang Ao, Jian Gao, Shuai Wang, Jia-Hao Jiang, Jie Deng, Hai-Kun Wang, Bei Xu, Jian-Yong Ding
Journal: Molecular Cancer (2023)

Abstract Immunotherapy has emerged to play a rapidly expanding role in the treatment of cancers. Currently, many clinical trials of therapeutic agents are on ongoing with majority of immune checkpoint inhibitors (ICIs) especially programmed death receptor 1 (PD-1) and its ligand 1 (PD-L1) inhibitors. PD-1 and PD-L1, two main immune checkpoints, are expressed at high levels in thymic epithelial tumors (TETs) and could be predictors of the progression and immunotherapeutic efficacy of TETs. However, despite inspiring efficacy reported in clinical trials and clinical practice, significantly higher incidence of immune-related adverse events (irAEs) than other tumors bring challenges to the administration of ICIs in TETs. To develop safe and effective immunotherapeutic patterns in TETs, understanding the clinical properties of patients, the cellular and molecular mechanisms of immunotherapy and irAEs occurrence are crucial. In this review, the progress of both basic and clinical research on immune checkpoints in TETs, the evidence of therapeutic efficacy and irAEs based on PD-1 /PD-L1 inhibitors in TETs treatment are discussed. Additionally, we highlighted the possible mechanisms underlying irAEs, prevention and management strategies, the insufficiency of current research and some worthy research insights. High PD-1/PD-L1 expression in TETs provides a rationale for ICI use. Completed clinical trials have shown an encouraging efficacy of ICIs, despite the high rate of irAEs. A deeper mechanism understanding at molecular level how ICIs function in TETs and why irAEs occur will help maximize the immunotherapeutic efficacy while minimizing irAEs risks in TET treatment to improve patient prognosis.
Implementation of the 7-1-7 target for detection, notification, and response to public health threats in five countries: a retrospective, observational study
Authors: Aaron F Bochner, Issa Makumbi, Olaolu Aderinola, Aschalew Abayneh, Ralph Jetoh, Rahel L Yemanaberhan, Jenom S Danjuma, Francis T Lazaro, Hani J Mahmoud, Trokon O Yeabah, Lydia Nakiire, Aperki K Yahaya, Renato A Teixeira, Mohammed Lamorde, Immaculate Nabukenya, John Oladejo, Ifedayo M O Adetifa, Wanderson Oliveira, Amanda McClelland, Christopher T Lee
Journal: The Lancet Global Health (2023)

Suboptimal detection and response to recent outbreaks, including COVID-19 and mpox (formerly known as monkeypox), have shown that the world is insufficiently prepared for public health threats. Routine monitoring of detection and response performance of health emergency systems through timeliness metrics has been proposed to evaluate and improve outbreak preparedness and contain health threats early. We implemented 7-1-7 to measure the timeliness of detection (target of ≤7 days from emergence), notification (target of ≤1 day from detection), and completion of seven early response actions (target of ≤7 days from notification), and we identified bottlenecks to and enablers of system performance.In this retrospective, observational study, we conducted reviews of public health events in Brazil, Ethiopia, Liberia, Nigeria, and Uganda with staff from ministries of health and national public health institutes. For selected public health events occurring from Jan 1, 2018, to Dec 31, 2022, we calculated timeliness intervals for detection, notification, and early response actions, and synthesised identified bottlenecks and enablers. We mapped bottlenecks and enablers to Joint External Evaluation (second edition) indicators.Of 41 public health events assessed, 22 (54%) met a target of 7 days to detect (median 6 days [range 0-157]), 29 (71%) met a target of 1 day to notify (0 days [0-24]), and 20 (49%) met a target of 7 days to complete all early response actions (8 days [0-72]). 11 (27%) events met the complete 7-1-7 target, with variation among event types. 25 (61%) of 41 bottlenecks to and 27 (51%) of 53 enablers of detection were at the health facility level, with delays to notification (14 [44%] of 32 bottlenecks) and response (22 [39%] of 56 bottlenecks) most often at an intermediate public health (ie, municipal, district, county, state, or province) level. Rapid resource mobilisation for responses (six [9%] of 65 enablers) from the national level enabled faster responses.The 7-1-7 target is feasible to measure and to achieve, and assessment with this framework can identify areas for performance improvement and help prioritise national planning. Increased investments must be made at the health facility and intermediate public health levels for improved systems to detect, notify, and rapidly respond to emerging public health threats.Bill & Melinda Gates Foundation.
Advances in haemostatic sponges: Characteristics and the underlying mechanisms for rapid haemostasis
Authors: Akriti Nepal, Huong D.N. Tran, Nam-Trung Nguyen, Hang Thu Ta
Journal: Bioactive Materials (2023)

In traumatized patients, the primary cause of mortality is uncontrollable continuous bleeding and unexpected intraoperative bleeding which is likely to increase the risk of complications and surgical failure. High expansion sponges are effective clinical practice for the treatment of wound bleeding (irregular/deep/narrow) that are caused by capillaries, veins and even arterioles as they possess a high liquid absorption ratio so can absorb blood platelets easily in comparison with traditional haemostasis treatments, which involve compression, ligation, or electrical coagulation etc. When in contact with blood, haemostatic sponges can cause platelet adhesion, aggregation, and thrombosis, preventing blood from flowing out from wounds, triggering the release of coagulation factors, causing the blood to form a stable polymerized fibre protein, forming blood clots, and achieving the goal of wound bleeding control. Haemostatic sponges are found in a variety of shapes and sizes. The aim of this review is to facilitate an overview of recent research around haemostatic sponge materials, products, and technology. This paper reviews the synthesis, properties, and characteristics of haemostatic sponges, together with the haemostasis mechanisms of haemostatic sponges (composite materials), such as chitosan, cellulose, gelatin, starch, graphene oxide, hyaluronic acid, alginate, polyethylene glycol, silk fibroin, synthetic polymers silver nanoparticles, zinc oxide nanoparticles, mesoporous silica nanoparticles, and silica nanoparticles. Also, this paper reviews commercial sponges and their properties. In addition to this, we discuss various in-vitro/in-vivo approaches for the evaluation of the effect of sponges on haemostasis.
Salt substitution and salt-supply restriction for lowering blood pressure in elderly care facilities: a cluster-randomized trial
Authors: Yifang Yuan, Aoming Jin, Bruce Neal, Xiangxian Feng, Qianku Qiao, Hongxia Wang, Ruijuan Zhang, Jiayu Li, Peifen Duan, La’e Cao, Hui Zhang, Senke Hu, Huijuan Li, Pei Gao, Gaoqiang Xie, Jianhui Yuan, Lili Cheng, Sujuan Wang, Haijun Zhang, Wenyi Niu, Hai Fang, Minghui Zhao, Runlin Gao, Junshi Chen, Paul Elliott, Darwin Labarthe, Yangfeng Wu
Journal: Nature Medicine (2023)
Global leadership is needed to optimize early childhood development for children with disabilities
Authors: Bolajoko O. Olusanya, Sheffali Gulati, Brad D. Berman, Mijna Hadders-Algra, Andrew N. Williams, Tracey Smythe, Nem Yun Boo, Nihad Almasri, Sandra S. Block, Cecilia Breinbauer, Sally Brinkman, Vivian G. Cheung, Adrian C. Davis, Marta Figueiredo, Lidia B. Giúdici, Melissa J. Gladstone, Toby M. Long, Paul Lynch, Marisol Moreno-Angarita, M. K. C. Nair, Felix A. Ogbo, Jacob O. Olusanya, Maureen E. Samms-Vaughan, Donald Wertlieb, Scott M. Wright
Journal: Nature Medicine (2023)
A swallowable X-ray dosimeter for the real-time monitoring of radiotherapy
Authors: Bo Hou, Luying Yi, Dehong Hu, Zichao Luo, Duyang Gao, Chao Li, Bowen Xing, Jiong-Wei Wang, Chuen Neng Lee, Rong Zhang, Zonghai Sheng, Bin Zhou, Xiaogang Liu
Journal: Nature Biomedical Engineering (2023)
Cancer and COVID-19: unravelling the immunological interplay with a review of promising therapies against severe SARS-CoV-2 for cancer patients
Authors: Yan Leyfman, Nancy Emmanuel, Gayathri P. Menon, Muskan Joshi, William B. Wilkerson, Jared Cappelli, Timothy K. Erick, Chandler H. Park, Pushpa Sharma
Journal: Journal of Hematology & Oncology (2023)

Abstract Cancer patients, due to their immunocompromised status, are at an increased risk for severe SARS-CoV-2 infection. Since severe SARS-CoV-2 infection causes multiple organ damage through IL-6-mediated inflammation while stimulating hypoxia, and malignancy promotes hypoxia-induced cellular metabolic alterations leading to cell death, we propose a mechanistic interplay between both conditions that results in an upregulation of IL-6 secretion resulting in enhanced cytokine production and systemic injury. Hypoxia mediated by both conditions results in cell necrosis, dysregulation of oxidative phosphorylation, and mitochondrial dysfunction. This produces free radicals and cytokines that result in systemic inflammatory injury. Hypoxia also catalyzes the breakdown of COX-1 and 2 resulting in bronchoconstriction and pulmonary edema, which further exacerbates tissue hypoxia. Given this disease model, therapeutic options are currently being studied against severe SARS-COV-2. In this study, we review several promising therapies against severe disease supported by clinical trial evidence—including Allocetra, monoclonal antibodies (Tixagevimab–Cilgavimab), peginterferon lambda, Baricitinib, Remdesivir, Sarilumab, Tocilizumab, Anakinra, Bevacizumab, exosomes, and mesenchymal stem cells. Due to the virus’s rapid adaptive evolution and diverse symptomatic manifestation, the use of combination therapies offers a promising approach to decrease systemic injury. By investing in such targeted interventions, cases of severe SARS-CoV-2 should decrease along with its associated long-term sequelae and thereby allow cancer patients to resume their treatments.
Stalled oligodendrocyte differentiation in IDH-mutant gliomas
Authors: Yanfei Wei, Guanzhang Li, Jing Feng, Fan Wu, Zheng Zhao, Zhaoshi Bao, Wei Zhang, Xiaodong Su, Jiuyi Li, Xueling Qi, Zejun Duan, Yunqiu Zhang, Sandra Ferreyra Vega, Asgeir Store Jakola, Yingyu Sun, Helena Carén, Tao Jiang, Xiaolong Fan
Journal: Genome Medicine (2023)

Abstract Background Roughly 50% of adult gliomas harbor isocitrate dehydrogenase ( IDH ) mutations. According to the 2021 WHO classification guideline, these gliomas are diagnosed as astrocytomas, harboring no 1p19q co-deletion, or oligodendrogliomas, harboring 1p19q co-deletion. Recent studies report that IDH-mutant gliomas share a common developmental hierarchy. However, the neural lineages and differentiation stages in IDH-mutant gliomas remain inadequately characterized. Methods Using bulk transcriptomes and single-cell transcriptomes, we identified genes enriched in IDH-mutant gliomas with or without 1p19q co-deletion, we also assessed the expression pattern of stage-specific signatures and key regulators of oligodendrocyte lineage differentiation. We compared the expression of oligodendrocyte lineage stage-specific markers between quiescent and proliferating malignant single cells. The gene expression profiles were validated using RNAscope analysis and myelin staining and were further substantiated using data of DNA methylation and single-cell ATAC-seq. As a control, we assessed the expression pattern of astrocyte lineage markers. Results Genes concordantly enriched in both subtypes of IDH-mutant gliomas are upregulated in oligodendrocyte progenitor cells (OPC). Signatures of early stages of oligodendrocyte lineage and key regulators of OPC specification and maintenance are enriched in all IDH-mutant gliomas. In contrast, signature of myelin-forming oligodendrocytes, myelination regulators, and myelin components are significantly down-regulated or absent in IDH-mutant gliomas. Further, single-cell transcriptomes of IDH-mutant gliomas are similar to OPC and differentiation-committed oligodendrocyte progenitors, but not to myelinating oligodendrocyte. Most IDH-mutant glioma cells are quiescent; quiescent cells and proliferating cells resemble the same differentiation stage of oligodendrocyte lineage. Mirroring the gene expression profiles along the oligodendrocyte lineage, analyses of DNA methylation and single-cell ATAC-seq data demonstrate that genes of myelination regulators and myelin components are hypermethylated and show inaccessible chromatin status, whereas regulators of OPC specification and maintenance are hypomethylated and show open chromatin status. Markers of astrocyte precursors are not enriched in IDH-mutant gliomas. Conclusions Our studies show that despite differences in clinical manifestation and genomic alterations, all IDH-mutant gliomas resemble early stages of oligodendrocyte lineage and are stalled in oligodendrocyte differentiation due to blocked myelination program. These findings provide a framework to accommodate biological features and therapy development for IDH-mutant gliomas.
Sotrovimab restores neutralization against current Omicron subvariants in patients with blood cancer
Authors: Mary Y. Wu, Scott T.C. Shepherd, Annika Fendler, Edward J. Carr, Lewis Au, Ruth Harvey, Giulia Dowgier, Agnieszka Hobbs, Lou S. Herman, Martina Ragno, Lorin Adams, Andreas M. Schmitt, Zayd Tippu, Benjamin Shum, Sheima Farag, Aljosja Rogiers, Nicola O’Reilly, Philip Bawumia, Callie Smith, Eleanor Carlyle, Kim Edmonds, Lyra Del Rosario, Karla Lingard, Mary Mangwende, Lucy Holt, Hamid Ahmod, Justine Korteweg, Tara Foley, Taja Barber, Stephanie Hepworth, Andrea Emslie-Henry, Niamh Caulfield-Lynch, Fiona Byrne, Daqi Deng, Bryan Williams, Michael Brown, Simon Caidan, Mike Gavrielides, James I. MacRae, Gavin Kelly, Kema Peat, Denise Kelly, Aida Murra, Kayleigh Kelly, Molly O’Flaherty, Sanjay Popat, Nadia Yousaf, Shaman Jhanji, Kate Tatham, David Cunningham, Nicholas Van As, Kate Young, Andrew J.S. Furness, Lisa Pickering, Rupert Beale, Charles Swanton, Sonia Gandhi, Steve Gamblin, David L.V. Bauer, George Kassiotis, Michael Howell, Susanna Walker, Emma Nicholson, James Larkin, Emma C. Wall, Samra Turajlic
Journal: Cancer Cell (2023)

Wu et al. report that patients with hematologic malignancies have reduced immunity against SARS-CoV-2 Omicron subvariants and Sotrovimab retains neutralizing capacity against all tested Omicron subvariants.
Re: Matthew S. Ernst, Vishal Navani, J. Connor Wells, et al. Outcomes for International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Groups in Contemporary First-line Combination Therapies for Metastatic Renal Cell Carcinoma. Eur Urol. 2023;84:109–116
Authors: Binghao Zhao, Hao Xing, Wenbin Ma
Journal: European Urology (2023)
Intracellular complement (complosome) is expressed in hematopoietic stem/progenitor cells (HSPCs) and regulates cell trafficking, metabolism and proliferation in an intracrine Nlrp3 inflammasome-dependent manner
Authors: Mariusz Z. Ratajczak, Mateusz Adamiak, Ahmed Abdelbaset-Ismail, Kamila Bujko, Arjun Thapa, Vira Chumak, Stephanie Franczak, Katarzyna Brzezniakiewicz-Janus, Janina Ratajczak, Magdalena Kucia
Journal: Leukemia (2023)
Clearance and production of ammonia quantified in humans by constant ammonia infusion – the effects of cirrhosis and ammonia-targeting treatments
Authors: Peter Lykke Eriksen, Lars Djernes, Hendrik Vilstrup, Peter Ott
Journal: Journal of Hepatology (2023)

Hyperammonaemia is a key pathological feature of liver disease and the primary driver of hepatic encephalopathy (HE). However, the relative roles of increased ammonia production and reduced clearance are poorly understood as is the action of ammonia-targeting drugs for HE. We aimed to quantify whole-body ammonia metabolism in healthy persons and patients with cirrhosis and to validate our method by examining the effects of glycerol phenylbutyrate and lactulose + rifaximin treatment.Ten healthy men and ten male patients with cirrhosis were investigated by 90-minute constant ammonia infusion to achieve steady-state plasma ammonia. Whole-body ammonia clearance was calculated as infusion rate divided by steady-state concentration increase and ammonia production was calculated as clearance multiplied by baseline ammonia concentration. Participants were re-investigated after the ammonia-targeting interventions.In healthy persons, ammonia clearance was 3.5 (3.1-3.9) L/min and ammonia production was 49 (35-63) μmol/min. Phenylbutyrate increased clearance by 11% (4-19%, p = 0.009). In patients with cirrhosis, ammonia clearance was 20% lower at 2.7 (2.1-3.3) L/min (p = 0.02) and production was nearly threefold higher at 131 (102-159) μmol/min (p <0.0001). Lactulose + rifaximin reduced production by 20% (2-37%, p = 0.03). The infusion was generally well-tolerated apart from in one hyperammonaemic patient, with cirrhosis and possible bleeding unrelated to the infusion, who developed clinical HE that reverted when infusion was discontinued.Whole-body ammonia clearance and production may be measured separately using the described technique. This technique identified a lower clearance and a higher production of ammonia in patients with cirrhosis, and showed that phenylbutyrate increases clearance, whereas lactulose + rifaximin reduces production.High blood ammonia plays a key role in cirrhosis-related brain dysfunction. However, the relative roles of reduced ammonia clearance and increased ammonia production are poorly understood as is the action of ammonia-targeting treatments. This study presents a relatively simple test to measure ammonia metabolism. By using this test, it was possible to show that patients with cirrhosis exhibit decreased ammonia clearance and increased ammonia production compared to healthy persons, and to quantify the unique effects of different ammonia-targeting treatments. The test described herein may be used to examine a range of questions related to normal physiology, pathophysiology and the mechanisms of action of ammonia-targeting treatments.ClinicalTrials.gov (1-16-02-297-20).
Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor in AML with MLL1-r or mutant NPM1
Authors: Warren Fiskus, Christopher P. Mill, Christine Birdwell, John A. Davis, Kaberi Das, Steffen Boettcher, Tapan M. Kadia, Courtney D. DiNardo, Koichi Takahashi, Sanam Loghavi, Michael J. Soth, Tim Heffernan, Gerard M. McGeehan, Xinjia Ruan, Xiaoping Su, Christopher R. Vakoc, Naval Daver, Kapil N. Bhalla
Journal: Blood Cancer Journal (2023)

Abstract Monotherapy with Menin inhibitor (MI), e.g., SNDX-5613, induces clinical remissions in patients with relapsed/refractory AML harboring MLL1-r or mtNPM1, but most patients either fail to respond or eventually relapse. Utilizing single-cell RNA-Seq, ChiP-Seq, ATAC-Seq, RNA-Seq, RPPA, and mass cytometry (CyTOF) analyses, present pre-clinical studies elucidate gene-expression correlates of MI efficacy in AML cells harboring MLL1-r or mtNPM1. Notably, MI-mediated genome-wide, concordant, log2 fold-perturbations in ATAC-Seq and RNA-Seq peaks were observed at the loci of MLL-FP target genes, with upregulation of mRNAs associated with AML differentiation. MI treatment also reduced the number of AML cells expressing the stem/progenitor cell signature. A protein domain-focused CRISPR-Cas9 screen in MLL1-r AML cells identified targetable co-dependencies with MI treatment, including BRD4, EP300, MOZ and KDM1A. Consistent with this, in vitro co-treatment with MI and BET, MOZ, LSD1 or CBP/p300 inhibitor induced synergistic loss of viability of AML cells with MLL1-r or mtNPM1. Co-treatment with MI and BET or CBP/p300 inhibitor also exerted significantly superior in vivo efficacy in xenograft models of AML with MLL1-r. These findings highlight novel, MI-based combinations that could prevent escape of AML stem/progenitor cells following MI monotherapy, which is responsible for therapy-refractory AML relapse.
Large-scale genome sequencing redefines the genetic footprints of high-altitude adaptation in Tibetans
Authors: Wangshan Zheng, Yaoxi He, Yongbo Guo, Tian Yue, Hui Zhang, Jun Li, Bin Zhou, Xuerui Zeng, Liya Li, Bin Wang, Jingxin Cao, Li Chen, Chunxia Li, Hongyan Li, Chaoying Cui, Caijuan Bai, None Baimakangzhuo, Xuebin Qi, None Ouzhuluobu, Bing Su
Journal: Genome biology (2023)

Tibetans are genetically adapted to high-altitude environments. Though many studies have been conducted, the genetic basis of the adaptation remains elusive due to the poor reproducibility for detecting selective signatures in the Tibetan genomes.
Correction: CD19/CD22 bispecific CAR-T cells for MRD-positive adult B cell acute lymphoblastic leukemia: a phase I clinical study
Authors: Jiahua Niu, Huiying Qiu, Fang Xiang, Lin Zhu, Jun Yang, Chongmei Huang, Kun Zhou, Yin Tong, Yu Cai, Baoxia Dong, Yuan Lu, Xuedong Sun, Liping Wan, Xueying Ding, Haopeng Wang, Xianmin Song
Journal: Blood Cancer Journal (2023)